The complications of diabetes mellitus continue to be a major source of morbidity and early morality. Type 1 diabetes, the subject of this application, contributes disproportionately to the health effects and health care costs of this disease. The prevalence, incidence and interrelationships of seven major complications (i.e., death, proliferative retinopathy, microalbuminuria, overt nephropathy, renal failure, neuropathy, and coronary and lower extremity arterial disease) of Type 1 diabetes and their risk factors have been examined in a 1-year prospective study of Type 1 diabetic subjects diagnosed in childhood. Risk factors and complication status have been determined on a biennial basis since baseline (1986-88). The investigators point out that this study population is a well defined cohort of Type 1 diabetic patients identified from Children's Hospital of Pittsburgh Registry and shown to be representative of the local county-wide diabetic population. All 658 study subjects have been diagnosed between 1950-80. Data collection will be complete in November 1998. Over 60 publications have reported on the prevalence, incidence and risk factors for complications in this population. Important links between blood pressure and neuropathy and lipoprotein concentrations and nephropathy have been identified. Extremely high rates of coronary artery disease, approaching 18% per year after 37 years of diabetes, have led to proposals in the new application to continue examination follow-up of those with long duration, i.e., 35+ years, Type 1 diabetes. A general survey follow-up will be continued until 2002 in all participants and further statistical analyses, including Markov Modeling and Tree Structured analysis, are planned. The genetic basis of complications will also be examined using a candidate gene approach using very specific detailed phenotyping of subjects according to their complication pattern. The effect of health care, access and type, and utilization on complication outcome will also be examined. A series of nested case controlled analyses will look at markers of oxidized lipoproteins and their role in predicting both cardiovascular and nephropathic outcomes. Homocysteine will also be studied in this manner. A particular focus will be on the role of Electron Beam Computerized Tomography (EBCT) as a screening tool for asymptomatic heart disease given the high cardiovascular mortality and morbidity in this population. Its predictive ability for future coronary events will be determined, as will the rate of progression of coronary calcification and its associated risk factors. The investigators state that this study will continue to advance our knowledge of the pathogenesis and prediction of complications of diabetes and lead to appropriate preventive strategies.